Interstitial cystitis (IC) is an idiopathic disease characterized by irritative voiding symptoms, pain, and characteristic bladder lesions seen on cystoscopic examination. The etiology and pathogenesis of the disease are unknown and no uniformly effective treatment is available. Some of the characteristics of IC, including the abrupt onset of symptoms in some patients, and the inflammatory changes seen in the bladder, are compatible with, and even suggestive of, and infective etiology of the disease. Recent studies have suggested that fastidious microorganisms, particularly Gardnerella vaginalis, may be associated with IC. Studies using modern molecular tools to detect and identify infectious agents in the bladder tissue or urine of IC patients have never been carried out. We propose to reexamine the role of infectious agents in the etiology of IC, using state-of-the-art molecular tools based on ribosomal RNA (rRNA) and polymerase chain reaction (PCR) technology. This unique approach supersedes all previous attempts to find infectious agents in these patients because it allows one to detect and identify any organism present in clinical specimens of IC patients with culture. Thus, the task of searching for fastidious organisms by laborious and difficult culture procedures is obviated by the use of specific oligonucleotide probes that are specific for these organisms. Furthermore, previously uncultured and undescribed bacteria can be identified using broad-range rRNA probes that will recognize any bacterial organism. These molecular techniques are now widely used in infectious disease studies, and they offer important advantages in studying a disease such as IC. They are highly specific, sensitive, and versatile; archival tissue, including frozen and paraffin-embedded tissue can be analyzed. Furthermore, samples such as urine and exfoliated bladder cells, which are obtained from IC patients by less invasive procedures of low morbidity, are suitable for this type of analysis. Our hypothesis is that fastidious or cryptic infectious agents may contribute to the etiology of IC. We propose to address this question using a molecular approach. We will: 1. Examine urine, bladder cells and biopsy samples from IC patients for the presence of fastidious organisms using rRNA-PCR techniques. 2. Search for previously uncultured organism in bladder tissue and urine of IC patients with rRNA-PCR procedures. 3. Study the virulence determinants of any fastidious organism identified in this study emphasizing the interaction of the organism with bladder cells.